Dutasteride, a synthetic 4-azasteroid compound, is an antiandrogen with the chemical name (5α,17β)-N-[2,5 bis(trifluoromethyl)phenyl]-3-oxo-4-azaandrost-1-ene-17-carboxamide. Dutasteride is indicated for the treatment of symptomatic benign prostate hyperplasia (BPH) in men with enlarged prostate glands. Dutasteride, a synthetic 4-azasteroid compound is a selective inhibitor of the type 1 and type 2 isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone. The empirical formula of Dutasteride is C27H30F6N2O2. Dutasteride is a white to off-white colored powder and stable under ordinary conditions. The melting point is 245° C.-245.5° C. Dutasteride is soluble in ethanol (44 mg/mL), methanol (64 mg/mL), and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water. Dutasteride has a partition coefficient, Log P=5.609±0.618.
Commercially available soft gel capsule formulations (e.g., Avodart®, which is produced by Glaxo Smithkline Pharmaceuticals), is a soft gelatin capsule used in the treatment of BPH, which contains 0.5 mg dutasteride dissolved in a mixture of mono/diglycerides of caprylic/capric acid (Capmul MCM) (349.5 mg) and butylated hydroxytoluene (0.035 mg). However, the manufacture of soft gel capsules is a slow and burdensome process, and therefore the manufacture of soft gel capsules is cost intensive and inefficient.
Consequently, there is a need for improved hard gel capsule formulations that reduce manufacturing costs, while maintaining the bioavailability and stability of the soft gel dosage forms.